Recent Advances in Exosomes as Drug Carriers

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 14236

Special Issue Editors


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Guest Editor
Institute for Chemical–Physical Processes (IPCF)–National Research Council Secondary Site (CNR SS), 70125 Bari, Italy
Interests: colloidal inorganic nanomaterials functionalization; lipid- and polymer-based nanosystems; drug delivery nanovectors; multifunctional targeted nanostructures; theranostics
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Guest Editor
National Institute of Gastroenterology, IRCCS DeBellis, 70013 Castellana Grotte, Italy
Interests: exosomes; nanovesicles; nanocarrier; gastrointestinal carcinogenesis; Wnt pathway

Special Issue Information

Dear Colleagues,

Exosomes are among the EVs that have been the most extensively studied, and are produced by cells exhibiting a variety of functions and targets. They are frequently utilized to transport therapeutic cargo for medical treatments and can be modified to improve their capacity for the distribution of drugs. In this Special Issue, we aim to highlight innovative works concerning the versatile capabilities of these vesicles to be used as natural nanoparticles for personalized medicine in the treatment of various pathologies.

As the Guest Editor of this Special Issue of Pharamaceutics (IF 6.525; https://www.mdpi.com/journal/Pharmaceutics), entitled “Recent Advances in Exosomes as Drug Carriers”, I invite you to submit your valuable contributions, in the form of original research articles and reviews. Research areas may include (but are not limited to) the following:

  • Exosome nanoformulation;
  • Exosome mimicry;
  • Exosomes as diagnostic tools.

I look forward to receiving your contributions.

Dr. Nicoletta Depalo
Dr. Maria Principia Scavo
Guest Editors

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Published Papers (5 papers)

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Research

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15 pages, 2167 KiB  
Article
Preparation of Nanoparticle-Loaded Extracellular Vesicles Using Direct Flow Filtration
by Shomit Mansur, Shahriar Habib, Mikayla Hawkins, Spenser R. Brown, Steven T. Weinman and Yuping Bao
Pharmaceutics 2023, 15(5), 1551; https://doi.org/10.3390/pharmaceutics15051551 - 20 May 2023
Cited by 3 | Viewed by 2987
Abstract
Extracellular vesicles (EVs) have shown great potential as cell-free therapeutics and biomimetic nanocarriers for drug delivery. However, the potential of EVs is limited by scalable, reproducible production and in vivo tracking after delivery. Here, we report the preparation of quercetin-iron complex nanoparticle-loaded EVs [...] Read more.
Extracellular vesicles (EVs) have shown great potential as cell-free therapeutics and biomimetic nanocarriers for drug delivery. However, the potential of EVs is limited by scalable, reproducible production and in vivo tracking after delivery. Here, we report the preparation of quercetin-iron complex nanoparticle-loaded EVs derived from a breast cancer cell line, MDA-MB-231br, using direct flow filtration. The morphology and size of the nanoparticle-loaded EVs were characterized using transmission electron microscopy and dynamic light scattering. The SDS-PAGE gel electrophoresis of those EVs showed several protein bands in the range of 20–100 kDa. The analysis of EV protein markers by a semi-quantitative antibody array confirmed the presence of several typical EV markers, such as ALIX, TSG101, CD63, and CD81. Our EV yield quantification suggested a significant yield increase in direct flow filtration compared with ultracentrifugation. Subsequently, we compared the cellular uptake behaviors of nanoparticle-loaded EVs with free nanoparticles using MDA-MB-231br cell line. Iron staining studies indicated that free nanoparticles were taken up by cells via endocytosis and localized at a certain area within the cells while uniform iron staining across cells was observed for cells treated with nanoparticle-loaded EVs. Our studies demonstrate the feasibility of using direct flow filtration for the production of nanoparticle-loaded EVs from cancer cells. The cellular uptake studies suggested the possibility of deeper penetration of the nanocarriers because the cancer cells readily took up the quercetin-iron complex nanoparticles, and then released nanoparticle-loaded EVs, which can be further delivered to regional cells. Full article
(This article belongs to the Special Issue Recent Advances in Exosomes as Drug Carriers)
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23 pages, 2849 KiB  
Article
Clinically Expired Platelet Concentrates as a Source of Extracellular Vesicles for Targeted Anti-Cancer Drug Delivery
by Ana Meliciano, Daniela Salvador, Pedro Mendonça, Ana Filipa Louro and Margarida Serra
Pharmaceutics 2023, 15(3), 953; https://doi.org/10.3390/pharmaceutics15030953 - 15 Mar 2023
Cited by 4 | Viewed by 2479
Abstract
The short shelf life of platelet concentrates (PC) of up to 5–7 days leads to higher wastage due to expiry. To address this massive financial burden on the healthcare system, alternative applications for expired PC have emerged in recent years. Engineered nanocarriers functionalized [...] Read more.
The short shelf life of platelet concentrates (PC) of up to 5–7 days leads to higher wastage due to expiry. To address this massive financial burden on the healthcare system, alternative applications for expired PC have emerged in recent years. Engineered nanocarriers functionalized with platelet membranes have shown excellent targeting abilities for tumor cells owing to their platelet membrane proteins. Nevertheless, synthetic drug delivery strategies have significant drawbacks that platelet-derived extracellular vesicles (pEV) can overcome. We investigated, for the first time, the use of pEV as a carrier of the anti-breast cancer drug paclitaxel, considering it as an appealing alternative to improve the therapeutic potential of expired PC. The pEV released during PC storage showed a typical EV size distribution profile (100–300 nm) with a cup-shaped morphology. Paclitaxel-loaded pEV showed significant anti-cancer effects in vitro, as demonstrated by their anti-migratory (>30%), anti-angiogenic (>30%), and anti-invasive (>70%) properties in distinct cells found in the breast tumor microenvironment. We provide evidence for a novel application for expired PC by suggesting that the field of tumor treatment research may be broadened by the use of natural carriers. Full article
(This article belongs to the Special Issue Recent Advances in Exosomes as Drug Carriers)
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Review

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30 pages, 2965 KiB  
Review
Unveiling the Potential of Extracellular Vesicles as Biomarkers and Therapeutic Nanotools for Gastrointestinal Diseases
by Valentina Arrè, Rita Mastrogiacomo, Francesco Balestra, Grazia Serino, Federica Viti, Federica Rizzi, Maria Lucia Curri, Gianluigi Giannelli, Nicoletta Depalo and Maria Principia Scavo
Pharmaceutics 2024, 16(4), 567; https://doi.org/10.3390/pharmaceutics16040567 - 21 Apr 2024
Cited by 3 | Viewed by 1744
Abstract
Extracellular vesicles (EVs), acting as inherent nanocarriers adept at transporting a range of different biological molecules such as proteins, lipids, and genetic material, exhibit diverse functions within the gastroenteric tract. In states of normal health, they participate in the upkeep of systemic and [...] Read more.
Extracellular vesicles (EVs), acting as inherent nanocarriers adept at transporting a range of different biological molecules such as proteins, lipids, and genetic material, exhibit diverse functions within the gastroenteric tract. In states of normal health, they participate in the upkeep of systemic and organ homeostasis. Conversely, in pathological conditions, they significantly contribute to the pathogenesis of gastrointestinal diseases (GIDs). Isolating EVs from patients’ biofluids facilitates the discovery of new biomarkers that have the potential to offer a rapid, cost-effective, and non-invasive method for diagnosing and prognosing specific GIDs. Furthermore, EVs demonstrate considerable therapeutic potential as naturally targeted physiological carriers for the intercellular delivery of therapeutic cargo molecules or as nanoscale tools engineered specifically to regulate physio-pathological conditions or disease progression. Their attributes including safety, high permeability, stability, biocompatibility, low immunogenicity, and homing/tropism capabilities contribute to their promising clinical therapeutic applications. This review will delve into various examples of EVs serving as biomarkers or nanocarriers for therapeutic cargo in the context of GIDs, highlighting their clinical potential for both functional and structural gastrointestinal conditions. The versatile and advantageous properties of EVs position them as promising candidates for innovative therapeutic strategies in advancing personalized medicine approaches tailored to the gastroenteric tract, addressing both functional and structural GIDs. Full article
(This article belongs to the Special Issue Recent Advances in Exosomes as Drug Carriers)
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30 pages, 1006 KiB  
Review
Exosomes: Potential Next-Generation Nanocarriers for the Therapy of Inflammatory Diseases
by Tosca Mori, Lisa Giovannelli, Anna Rita Bilia and Francesca Margheri
Pharmaceutics 2023, 15(9), 2276; https://doi.org/10.3390/pharmaceutics15092276 - 4 Sep 2023
Cited by 8 | Viewed by 3284
Abstract
Inflammatory diseases are common pathological processes caused by various acute and chronic factors, and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e., cytoskeletal and cytosolic proteins (actin, tubulin, [...] Read more.
Inflammatory diseases are common pathological processes caused by various acute and chronic factors, and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e., cytoskeletal and cytosolic proteins (actin, tubulin, and histones), nucleic acids (mRNA, miRNA, and DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, and ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, and adhesion molecules). This review will be a synopsis of the knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, and liver and kidney injuries. Current knowledge indicates that the role of exosomes in the therapy of inflammation and in inflammatory diseases could be distinctive. The main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of the selection of exosomes; their dosages and routes of administration; and a deeper knowledge about their biodistribution, type and incidence of adverse events, and long-term effects of exosomes. In conclusion, exosomes can be a very promising next-generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile, and selective delivery systems in the future. Full article
(This article belongs to the Special Issue Recent Advances in Exosomes as Drug Carriers)
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27 pages, 3350 KiB  
Review
Radiolabelled Extracellular Vesicles as Imaging Modalities for Precise Targeted Drug Delivery
by Sumel Ashique and Krishnan Anand
Pharmaceutics 2023, 15(5), 1426; https://doi.org/10.3390/pharmaceutics15051426 - 6 May 2023
Cited by 7 | Viewed by 2968
Abstract
Extracellular vesicles (ECVs) have been abandoned as bio-inspired drug delivery systems (DDS) in the biomedical field. ECVs have a natural ability to cross over extracellular and intracellular barriers, making them superior to manufactured nanoparticles. Additionally, they have the ability to move beneficial biomolecules [...] Read more.
Extracellular vesicles (ECVs) have been abandoned as bio-inspired drug delivery systems (DDS) in the biomedical field. ECVs have a natural ability to cross over extracellular and intracellular barriers, making them superior to manufactured nanoparticles. Additionally, they have the ability to move beneficial biomolecules among far-flung bodily cells. These advantages and the accomplishment of favorable in vivo results convincingly show the value of ECVs in medication delivery. The usage of ECVs is constantly being improved, as it might be difficult to develop a consistent biochemical strategy that is in line with their useful clinical therapeutic uses. Extracellular vesicles (ECVs) have the potential to enhance the therapy of diseases. Imaging technologies, particularly radiolabelled imaging, have been exploited for non-invasive tracking to better understand their in vivo activity. Full article
(This article belongs to the Special Issue Recent Advances in Exosomes as Drug Carriers)
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